Neovascularization is a characteristic phenomenon associated with a number of ocular disorders. Of these proliferative diabetic retinopathy is the most prevalent and has become the leading cause of newly diagnosed blindness. Theoretically the growth of a blood vessel is regulated by a number of processes, namely endothelial cell proliferation, invasion and chemotaxis. This proposal is aimed at elucidating the role of inhibitors of endothelial cell proliferation in blood vessel growth. We have identified and partially characterized two inhibitors of endothelial cell proliferation: one from cartilage (EGI) and one from the media of confluent endothelial cell cultures (EC-chalone). This proposal is designed to elucidate the mode of action of these inhibitors at the cellular level, and to determine whether they are useful therapeutic agents as in vivo inhibitors of blood vessel growth using a model of corneal neovascularization. Furthermore we plan to purify and characterize these inhibitors as to their stability and distribution in ocular structures using various routes of administration. These studies will provide not only an understanding of the signals which regulate the growth and final architecture of the vascular bed, but will also define whether it is possible to use natural inhibitors of endothelial cell proliferaion to control neovascularization in vivo.